NICHE-3: Growing Evidence for Immune Checkpoint Inhibitors in MMR-Deficient Colorectal Cancer

Data from NICHE-3 showed that neoadjuvant nivolumab plus relatlimab (nivo/rela), an immune checkpoint inhibitor (ICI), led to a pathologic response rate of 96% in patients with MMR-deficient (dMMR) colorectal cancer (CRC), according to results presented at European Society for Medical Oncology Congress 2024. The study was conducted by Peter de Gooyer, MD, and colleagues.

Fifty-nine patients with dMMR CRC were treated with two doses of nivo/rela (480 mg/480 mg) on days one and 29, followed by surgery within eight weeks of enrollment. Pathologic response was defined as ≤50% residual viable tumor (RVT). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR) (≤10% RVT), safety, and survival.

The median patient age was 65 years, and 78% of patients had clinical stage 3 disease. Of the 59 patients, 56 have undergone surgery, and surgery is scheduled for three more treated patients. Pathologic response was observed in 54 of 56 patients (96%) and included 91% MPR and 68% pCR. This pCR rate is similar to the response rate observed with nivo plus ipilimumab.

Grade 3-4 immune-related adverse events were observed in six patients (10%) and led to delay of surgery in three. Endocrinopathies requiring long-term suppletion occurred in 14 (24%) patients consisting of 10 cases of hypothyroidism (17%) and five (8%) of adrenal insufficiency. To date, one patient experienced disease recurrence.

“This study adds to a growing body of evidence of the role of ICI in dMMR CRC and provides a basis for larger studies and exploration of organ-sparing strategies,” the researchers wrote.